This research project has three closely related objectives: to define the biochemical and genetic mechanisms which regulate transmembrane transport of amino acids and hexoses; to understand how such transport mechanisms control and are controlled by intracellular metabolic pathways for these compounds; and to translate these observations of cellular phenomena into diagnostic, pathogenetic, and therapeutic programs for selected inherited and acquired human disease states. To approach these objectives, the role of ions, vitamins, hormones and other metabolites which modulate membrane and/or intracellular reactions will be examined. A variety of experimental designs in vivo and in vitro will be employed. In some instances, crucial answers will come from the study of the sick patient; in others from the investigation of the healthy animal. The predictive power of the genetic approach will be utilized as will the resolving power of studies of isolated membranes or enzymes. Regardless of the point of departure, we shall strive to make the basic biological phenomena relevant to an understanding of cellular and human physiology and pathophysiology.